Dendritic spine density a measure of cognitive reserveDocument Transcript
Dendritic Spine Density a Measure of Cognitive Reserve?The cognitive reserve hypothesis is a heuristic concept used to explain apparent protection fromthe onset of cerebral disease and/or cognitive decline in old age. This hypothesis explains thedisparity between clinical and pathological phenotypes and why, in two individuals with thesame extent of neuropathology, one may be demented while the other remains cognitivelyintact.Most neuroprotective agents are thought to exercise their action by promoting dendritic spinegrowth. Although this is accomplished by different mechanisms, the neuroprotective power ofan agent can be assessed by its ability to increase dendritic spine density. Measuring dendriticspine density in cultured neurons from patients with various neuropsychiatric conditions mightgive us an idea of an individual’s cognitive reserve.Neuropathological studies have demonstrated that a number of disease states, ranging fromschizophrenia to autism spectrum disorders, display abnormal dendritic spine morphology ornumbers. Moreover, recent genetic studies have identified mutations in numerous genes thatencode synaptic proteins, leading to suggestions that these proteins may contribute to aberrantspine plasticity that, in part, underlie the pathophysiology of these disordershttp://www.ncbi.nlm.nih.gov/pubmed/18535839A Software able to measure dendritic density:Uncovering the mechanisms that regulate dendritic spine morphology has been limited, in thepast by the lack of efficient and unbiased methods for analyzing spines.The discovery of automated 3D and 4D spine morphometry softwares, like Imaris, lead to theability of indirect measurement of cognitive capacity in the near future. The module FilamentTracer, in the Imaris software can be used to automatically detect and measure spines across alarge dataset. This video explains how:http://www.youtube.com/watch?v=9jQ0byergiw&feature=relmfuMeasuring Dendritic Spine Density in Cultured NeuronsPatient-specific neurons can be obtained by cellular reprogramming either via inducedpluripotent stem cells (IPSC) or more recently by lineage reprogramming (also calledtransdifferentiation). The latter reprogramming method provides a fast route for creatingnovel cell types and manufacturing functional tissues. TD enables the generation ofpatient-specific cell types without the risk of creating potentially tumorigenic inducedpluripotent stem cells before differentiation. TD starts from fibroblasts and uses“stemness factors” that are either microRNAs, transcription factors or both.
Once patient specific neurons have been created, they are allowed to form networks. On June 7,2012, scientists at the UCSF-affiliated Gladstone Institutes have for the first time transformedskin cells into cells that develop on their own into an interconnected, functional network ofbrain cells. The next step could be determining dendritic spine density in neurons obtained bytransdifferentiation. This video illustrates the advantages of studying patient specific neurons.http://www.youtube.com/watch?v=IU7iAf-YSFgADONIS SFERA, MD